A STUDY OF THE EFFECTIVENESS OF A CARCINOSTATIC AND INCREASING GARCINOSTATIC TOLERANCE
Grant-in-Aid for General Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Tokai University|
MITOMI Toshio Tokai University school of Medicine, General Surgery, Professor, 医学部・外科学, 教授 (20055809)
WATANABE Keiichi Tokai University school of Medicine, Pathology, Professor, 医学部・病理学, 教授 (00055865)
NAKASAKI Hisao Tokai University school of Medicine, General Surgery, Assistant Professor, 医学部・外科学, 助教授 (10056145)
|Project Period (FY)
1994 – 1995
Completed(Fiscal Year 1995)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥1,300,000 (Direct Cost : ¥1,300,000)
|Keywords||anti cancer drug / antibody-anti cancer drug / side effect / 薬効作用|
Background of the study
Drug resistance in chemotherapy can be pharmacologically classified into one based on membrane resistance and another based on enzyme resistance . Studies have been conducted to elucidate these resistance phenomena and develop new therapeutic agents but the outcomes are not yet totally satisfactory. Some drugs are employed frequently due to their therapeutic efficacy but the eventual emergence of resistance necessitates the use of multiple agents and efforts to confront the multiple adverse affects. Thus studies have also been conducted to overcome resistance by the combined use of both antineoplastic and non-antineoplastic agents. A more effective outcome may be expected from the therapeutic modality if resistance is suppressed or its development delayd before the antineoplastic agents meet resistance, rather than investigating cancer that has already developed resistance. Our study was based on this viewpoint.
Process and outcome of the study
In this study, we us
ed antineoplastic and non-antineoplastic agents. We succeeded in preparing an antibody by immunizing rabbits against ADM (adriamycin). By using this antibody directed against the antineoplastic agent, we expected to inactivate intentionally the activity of the antineoplastic agent that has been administered, thus achieving a more effective chemotherapy. In animal experiments, we observed evident potentiation of the effect of the antineoplastic agent. Furthermore this designed inactivation enabled rerductions in the adverse effects of the antineoplastic agent. The most out-standing adverse effect related to ADM is cardiotoxicity, which was amelioratedby the combined use of anti-adria-mycin antibody, permitting administration of a greater dosage of the antineoplastic agent.
(1) Preparation of an antibody by using ADM.
The resultant anti-ADM antibody is a polyclonal IgG antibody with a molecular weight of 150,000, which has a specificity to ADM.
(2) A lack of cross reactivity and the specificity of the reaction of the anti-ADM antibody to ADM, in spite of the presence of the ubiquinone rings, such as that of ADM, in the cell membrane and Co-Q10.
(3) Immunohistochemical observation of the localization of ADM in the cancerous tissue, by using the anti-ADM antibody.
(4) A study on changes and localization of carbohydrate chain antigens in the cell membrane of cancerous tissue.
(5) Report on the research on inactivation of the pharmacological action of ADM by the anti-ADM antibody.
(6) Repeated administration of the anti-ADM antibody to rats. Confirmation of the efficacy of the antibodies in the treatment of transplanted neoplasms. Less
Research Products (2results)